Muhammet Uyanik

Quaternary Ammonium (Hypo)iodite Catalysis for Enantioselective Oxidative Cycloetherification

Eye for an I Oxidative catalysis is largely the domain of transition metals, whether iron in an enzyme, or rarer palladium in a synthetic system. These metals can efficiently shuttle between oxidation states, easing the transfer of hydrogen and oxygen atoms between hydrocarbons and oxidants. Uyanik et al. (p. 1376; see the Perspective by French) now show that iodine can take the place of the metal to catalytically activate peroxide during the formation of benzofuran derivatives. Pairing iodide anions with chiral ammonium cations allowed the generation of stereoselectivity at levels similar to those seen with metal complexes bearing chiral ligands. Iodine can effectively replace a transition metal as an electron-transfer catalyst for an organic reaction. It is desirable to minimize the use of rare or toxic metals for oxidative reactions in the synthesis of pharmaceutical products. Hypervalent iodine compounds are environmentally benign alternatives, but their catalytic use, particularly for asymmetric transformations, has been quite limited. We report here an enantioselective oxidative cycloetherification of ketophenols to 2-acyl-2,3-dihydrobenzofuran derivatives, catalyzed by in situ–generated chiral quaternary ammonium (hypo)iodite salts, with hydrogen peroxide as an environmentally benign oxidant. The optically active 2-acyl 2,3-dihydrobenzofuran skeleton is a key structure in several biologically active compounds.

In Situ Generated (Hypo)Iodite Catalysts for the Direct α-Oxyacylation of Carbonyl Compounds with Carboxylic Acids†

a-Acyloxycarbonyl compounds, which are significant building blocks in synthetic organic chemistry, can traditionally be prepared by the substitution reaction of a-halocarbonyl compounds with alkaline carboxylates or the direct oxidative coupling of carbonyl compounds with toxic heavy metal oxidants (i.e. Pb(OAc)4, Tl(OAc)3, Mn(OAc)3, etc.). [2] Recently, the chiral amine catalyzed enantioselective aoxybenzoylation of aldehydes with benzoyl peroxide has also been reported. However, the substrate scope is still limited. Although hypervalent iodine compounds are environmentally benign alternatives to rare or toxic heavy metal oxidants, their use in catalytic amounts is still limited. In 2005, the groups of Ochiai and Kita independently reported the first iodosoarene (ArIL2)-catalyzed oxidative coupling reactions using meta-chloroperbenzoic acid (mCPBA) as a co-oxidant. In particular, Ochiai et al. developed the a-oxyacetylation of ketones catalyzed by the in situ generated iodine(III) in the presence of an excess amount of BF3·Et2O in wet acetic acid [Eq. (1)]. [5a] In 2007,

2-Iodoxybenzenesulfonic Acid as an Extremely Active Catalyst for the Selective Oxidation of Alcohols to Aldehydes, Ketones, Carboxylic Acids, and Enones with Oxone

Electron-donating group-substituted 2-iodoxybenzoic acids (IBXs) such as 5-Me-IBX (1g), 5-MeO-IBX (1h), and 4,5-Me(2)-IBX (1i) were superior to IBX 1a as catalysts for the oxidation of alcohols with Oxone (a trademark of DuPont) under nonaqueous conditions, although Oxone was almost insoluble in most organic solvents. The catalytic oxidation proceeded more rapidly and cleanly in nitromethane. Furthermore, 2-iodoxybenzenesulfonic acid (IBS, 6a) was much more active than modified IBXs. Thus, we established a highly efficient and selective method for the oxidation of primary and secondary alcohols to carbonyl compounds such as aldehydes, carboxylic acids, and ketones with Oxone in nonaqueous nitromethane, acetonitrile, or ethyl acetate in the presence of 0.05-5 mol % of 6a, which was generated in situ from 2-iodobenzenesulfonic acid (7a) or its sodium salt. Cycloalkanones could be further oxidized to alpha,beta-cycloalkenones or lactones by controlling the amounts of Oxone under the same conditions as above. When Oxone was used under nonaqueous conditions, Oxone wastes could be removed by simple filtration. Based on theoretical calculations, we considered that the relatively ionic character of the intramolecular hypervalent iodine-OSO(2) bond of IBS might lower the twisting barrier of the alkoxyperiodinane intermediate 16.

Catalysis with In Situ‐Generated (Hypo)iodite Ions for Oxidative Coupling Reactions

This Concept highlights the discovery and development of oxidative coupling reactions catalyzed by the hypoiodite (IO−) or iodite (OIO−) ion, which are generated in situ from iodide (I−) ion with hydrogen peroxide or tert‐butyl hydroperoxide as an environmentally benign oxidant. The most important features of these catalytic systems are 1) metal‐free oxidation, 2) milder reaction conditions, 3) high chemoselectivity (they tolerate a wide range of various functional groups), 4) operational simplicity, and 5) water or tert‐butyl alcohol as the only byproduct derived from the co‐oxidant used.

High-turnover hypoiodite catalysis for asymmetric synthesis of tocopherols

Iodine blooms as an oxidation catalyst Most catalysts for organic oxidation chemistry—whether biochemical or artificial—contain a transition metal like iron or palladium. Uyanik et al. now show that iodine can take the place of a metal in catalyzing efficient oxidative ring closures to make chromans—hexagonal rings incorporating oxygen that are perhaps best known as a constituent of the vitamin E structure (see the Perspective by Nachtsheim). The iodine is added as a salt with a chiral cation, which directs the reaction to form just one of two possible mirror-image variants of the product. Key to the success of the system was the addition of a base, which maintained the viability of an unstable, partially oxidized iodine intermediate critical to the reaction cycle. The results bode well for more general use of iodine salts as asymmetric oxidation-reduction catalysts. Science, this issue p. 291; see also p. 270 An iodide salt with a chiral counterion proves an efficient catalyst for preparation of compounds analogous to vitamin E. [Also see Perspective by Nachtsheim] The diverse biological activities of tocopherols and their analogs have inspired considerable interest in the development of routes for their efficient asymmetric synthesis. Here, we report that chiral ammonium hypoiodite salts catalyze highly chemo- and enantioselective oxidative cyclization of γ-(2-hydroxyphenyl)ketones to 2-acyl chromans bearing a quaternary stereocenter, which serve as productive synthetic intermediates for tocopherols. Raman spectroscopic analysis of a solution of tetrabutylammonium iodide and tert-butyl hydroperoxide revealed the in situ generation of the hypoiodite salt as an unstable catalytic active species and triiodide salt as a stable inert species. A high-performance catalytic oxidation system (turnover number of ~200) has been achieved through reversible equilibration between hypoiodite and triiodide in the presence of potassium carbonate base. We anticipate that these findings will open further prospects for the development of high-turnover redox organocatalysis.

IBS-catalyzed oxidative rearrangement of tertiary allylic alcohols to enones with oxone.

A 2-iodoxybenzenesulfonic acid (IBS)-catalyzed oxidative rearrangement of tertiary allylic alcohols to enones with powdered Oxone in the presence of potassium carbonate and tetrabutylammonium hydrogen sulfate has been developed.

Hypervalent iodine-catalyzed oxylactonization of ketocarboxylic acids to ketolactones.

The hypervalent iodine-catalyzed oxylactonization of ketocarboxylic acids to ketolactones was achieved in the presence of iodobenzene (10 mol%), p-toluenesulfonic acid monohydrate (20 mol%) and meta-chloroperbenzoic acid as a stoichiometric co-oxidant.

IBS-Catalyzed Regioselective Oxidation of Phenols to 1,2-Quinones with Oxone®

We have developed the first example of hypervalent iodine(V)-catalyzed regioselective oxidation of phenols to o-quinones. Various phenols could be oxidized to the corresponding o-quinones in good to excellent yields using catalytic amounts of sodium salts of 2-iodobenzenesulfonic acids (pre-IBSes) and stoichiometric amounts of Oxone® as a co-oxidant under mild conditions. The reaction rate of IBS-catalyzed oxidation under nonaqueous conditions was further accelerated in the presence of an inorganic base such as potassium carbonate (K2CO3), a phase transfer catalyst such as tetrabutylammonium hydrogen sulfate (nBu4NHSO4), and a dehydrating agent such as anhydrous sodium sulfate (Na2SO4).

Bromine-catalyzed aerobic oxidation of alcohols.

The oxidation of alcohols to the corresponding carbonyl compounds is one of the most fundamental and important transformations in synthetic organic chemistry. Molecular oxygen is the most ideal oxidant because it is both atomeconomically and environmentally benign. To date, numerous transition-metal-catalyzed aerobic oxidations of alcohols have been developed. Recently, the TEMPO (a nitroxy radical)-catalyzed aerobic oxidation of alcohols has also been reported. However, there is a strong need for cheaper, more efficient, more chemoselective, and greener methods for such transformations, particularly in the pharmaceutical industry. Over the past two decades, hypervalent iodine compounds have been the focus of considerable attention, owing to their mild and chemoselective oxidizing properties and their environmentally benign character in contrast to toxic-metal reagents. Very recently, we reported a highly-efficient and chemoselective oxidation of various alcohols to carbonyl compounds, such as aldehydes, carboxylic acids, and ketones with powdered Oxone (2 KHSO5·KHSO4·K2SO4) in the presence of catalytic amounts of 2-iodoxybenzenesulfonic acid (IBS), which is generated in situ from 2-iodobenzenesulfonic acid (Scheme 1). On the other hand, Liu and co-workers reported a hypervalent iodine-catalyzed oxidation of alcohols using molecular oxygen as a terminal oxidant. Accordingly, the aerobic oxidation of a broad range of primary and secondary alcohols to aldehydes and ketones, respectively, in water was effectively catalyzed by iodoxybenzene (PhIO2, 1 mol %) in the presence of catalytic amounts of Br2 and NaNO2 (Scheme 2). The catalytic mechanism they proposed for this reaction involves three redox cycles (Scheme 3). PhIO2 is the active oxidant that oxidizes the alcohol to the corresponding carbonyl compound, and is reduced to dihydroxyiodobenzene (PhI(OH)2). PhI(OH)2 is reoxidized to PhIO2 with Br2, which is reduced to HBr. The oxidation of NO with O2 produces NO2, which re-oxidizes HBr to Br2. In addition, HNO3 produced by dissolving NO2 in water can also oxidize HBr to Br2.

Baeyer–Villiger Oxidation and Oxidative Cascade Reactions with Aqueous Hydrogen Peroxide Catalyzed by Lipophilic Li[B(C6F5)4] and Ca[B(C6F5)4]2

Efficient and selective: Two lipophilic catalysts were used for Baeyer-Villiger (BV) oxidations to give lactones in high yields. Cascade reactions involving this BV oxidation were used to selectively obtain either unsaturated carboxylic acids or hydroxylactones in high yields from β-silyl cyclohexanones.